Inflammatory Bowel Disease Types Differ in Markers of Inflammation, Gut Barrier and in Specific Anti-Bacterial Response

Abstract

Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC-IBD), share three major pathogenetic mechanisms of inflammatory bowel disease (IBD)-gut dysbiosis, gut barrier failure and immune system dysregulation. While clinical differences among them are well known, the underlying mechanisms are less explored. To gain an insight into the IBD pathogenesis and to find a specific biomarker pattern for each of them, we used protein array, ELISA and flow cytometry to analyze serum biomarkers and specific anti-microbial B and T cell responses to the gut commensals. We found that decrease in matrix metalloproteinase (MMP)-9 and increase in MMP-14 are the strongest factors discriminating IBD patients from healthy subjects and that PSC-IBD patients have higher levels of Mannan-binding lectin, tissue inhibitor of metalloproteinases 1 (TIMP-1), CD14 and osteoprotegerin than patients with UC. Moreover, we found that low transforming growth factor-β1 (TGF-β1) is associated with disease relapse and low osteoprotegerin with anti-tumor necrosis factor-alpha (TNF-α) therapy. Patients with CD have significantly decreased antibody and increased T cell response mainly to genera Eubacterium, Faecalibacterium and Bacteroides. These results stress the importance of the gut barrier function and immune response to commensal bacteria and point at the specific differences in pathogenesis of PSC-IBD, UC and CD.

Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier Dysfunction

“…Hypersensitivity is driven by peripheral and central mechanisms [42], involving the participation of the intestinal wall, spinal cord, and brain centers [43]. Nonetheless, contemporary histopathology studies in IBD patients, as well as the established murine models of intestinal inflammation, implicate a causative combination of progressive destruction of the intestinal mucosal barrier and altered mucosal immune responses [44].…”

Intestinal Microbes in Autoimmune and Inflammatory Disease

“…In IBD patients, there are reductions in potentially anti-inflammatory microbes such as Bacteroidetes, Lachnospiraceae (16), and Faecalibacterium prausnitzii (31,32) alongside increases in potentially inflammatory microbes such as Proteobacteria and Ruminococcus gnavus (30,(33)(34)(35)(36)(37)(38)(39). Further, increased mucosa-associated bacteria (16,40) results in greater contact between gut microbes and immune system and leads to anti-bacterial immunity associated with IBD pathogenesis (41)(42)(43)(44)(45).…”

Urinary I-FABP, L-FABP, TFF-3, and SAA Can Diagnose and Predict the Disease Course in Necrotizing Enterocolitis at the Early Stage of Disease

“…TFF-3 is elevated in patients with severe sepsis and inflammatory bowel diseases. TFF-3 levels correlate with the activity of ulcerative colitis localized to the colonic mucosa, suggesting the site-specific upregulation of TFF-3 in inflamed colonic mucosa [24][25][26]. Moreover, it was shown that TFF-3 was associated with protective effect on intestinal tract injury in animal model of NEC via protection of excessive apoptosis by the increase of Bcl-2 and reduction of caspase-3 and Bax expression [27].…”